CORIMUNO-ANA: Trial Evaluating Efficacy Of Anakinra In Patients With Covid-19 Infection

Assistance Publique - Hôpitaux de Paris

Status and phase: Completed; Phase 2

Conditions: Corona Virus Infection

Treatments: Drug: Anakinra

Study type: Interventional

Funder types: Other

Identifiers

NCT04341584

APHP200375-5

Details and patient eligibility

About

The overall objective of the study is to determine the therapeutic effect and tolerance of Anakinra in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Anakinra (ANA) is a recombinant human decoy IL-1Ra and therefore blocks IL-1α and IL-1β. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Anakinra administration to patients enrolled in the CORIMUNO-19 cohort. Anakinra will be administered to consenting adult patients hospitalized with CORVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation. Patients who will chose not to receive Anakinra will receive standard of cares. Outcomes of Anakinra -treated patients will be compared with outcomes of standard of care treated patients as well as outcomes of patients treated with other immune modulators.

Enrollment: 161 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients included in the CORIMUNO-19 cohort

2. Patients with C-reactive protein level (CRP) > 25 mg / L the day or the day before the infusion)

3. Patients belonging to one of the 2 following groups:

   • Group 1: patients meeting all of the following criteria: 1) Requiring more than 3L/min of oxygen; 2) WHO progression scale = 5; 3) No non invasive ventilation or High flow
   • Group 2: patients with respiratory failure AND (requiring mechanical ventilation OR non invasive ventilation OR High flow), with a WHO progression scale ≥ 6, and no do-not-resuscitate (DNR) order

Exclusion criteria

• Patients with exclusion criteria to the CORIMUNO-19 cohort.

• Known hypersensitivity to Anakinra or to any of their excipients.

• Pregnancy

• Current documented bacterial infection.

• Patient with any of following laboratory results out of the ranges detailed below at screening:

  • Absolute neutrophil count (ANC) ≤ 1.0 x 109/L
  • Haemoglobin level: no limitation
  • Platelets (PLT) < 50 G /L
  • SGOT or SGPT > 5N
  • Severe renal insufficiency with Glomerular filtration rate < 30 ml / mn

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

161 participants in 4 patient groups

ANAKINRA -- Severe COVID Population (WHO-Clinical Progression Scale =5 at baseline)

Experimental group

Description:

Treatment includes the administration of Two IV infusions / day of ANAKINRA KINERET® 200mg (Total 400 mg) at day 1 (D1), D2 and D3, two IV infusions / day of ANAKINRA KINERET® 100mg (Total 200 mg) at day 4 (D4), and one IV infusion of ANAKINRA KINERET® 100mg (Total 100 mg) at day 5 (D5). In case of absence of improvement at D4 (absence of clinical improvement AND absence of decrease of CRP level \> 50%), 3 supplementary days of treatment at 400 mg/day will be done at D4, D5, D6 followed by a decrease at 200 mg/day at D7 and 100 mg/day at D8 and stop thereafter

Treatment:

Drug: Anakinra

Standard of care -- Severe COVID Population (WHO-Clinical Progression Scale =5 at baseline)

No Intervention group

ANAKINRA -- Critical COVID Population (WHO-Clinical Progression Scale >5 at baseline)

Experimental group

Description:

Treatment includes the administration of Two IV infusions / day of ANAKINRA KINERET® 200mg (Total 400 mg) at day 1 (D1), D2 and D3, two IV infusions / day of ANAKINRA KINERET® 100mg (Total 200 mg) at day 4 (D4), and one IV infusion of ANAKINRA KINERET® 100mg (Total 100 mg) at day 5 (D5). In case of absence of improvement at D4 (absence of clinical improvement AND absence of decrease of CRP level \> 50%), 3 supplementary days of treatment at 400 mg/day will be done at D4, D5, D6 followed by a decrease at 200 mg/day at D7 and 100 mg/day at D8 and stop thereafter

Treatment:

Drug: Anakinra

Standard of care -- Critical COVID Population (WHO-Clinical Progression Scale >5 at baseline)

No Intervention group